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Biomedical subjects

H Gylling

Publications and source records attributed to H Gylling.

At least 55 records · Page 3Linked to original sources
PubMed1999

Serum squalene in postmenopausal women without and with coronary artery disease.

Squalene, found in earlier studies in human atherosclerotic plaques, was measured in the serum of postmenopausal women with coronary artery disease (CAD) (n = 25) and randomly chosen age-matched healthy controls (n = 30). The squalene concentrations of the whole population ranged from 37.5 to 115.5 microg/dl, and were higher in serum of the CAD than healthy women (91.4+/-2.6 versus 65.2+/-2.6 microg/dl, P = 0.000), a finding observed also in relation to cholesterol (43.8+/-1.8 versus 32.9+/-1.1 10(2)x mmol/mol of cholesterol, P = 0.000). The squalene concentration was also increased in chylomicrons, VLDL and d>1.006 g/ml lipoproteins, and the proportions to cholesterol in VLDL and d>1.006 g/ml lipoproteins. The respective squalene and cholesterol concentrations were related to each other in serum, VLDL and d>1.006 g/ml lipoproteins (r = 0.52, 0.85 and 0.55, respectively), whereas the correlation with triglycerides was seen only in VLDL (r = 0.84) over the whole population. Besides enhanced intestinal secretion, it remains to be shown whether higher serum squalene in postmenopausal coronary women is due to increased cholesterol synthesis or a defect in squalene conversion to lanosterol.

Biomarkers↗
PubMed1999

Cholesterol reduction by different plant stanol mixtures and with variable fat intake.

Our aim was to investigate (1) whether different campestanol/sitostanol mixtures in margarine differ in reducing serum cholesterol, and (2) whether sitostanol ester in butter decreases serum cholesterol and alters cholesterol absorption and metabolism. Twenty-three postmenopausal women replaced 25 g dietary fat with (1) sitostanol ester-rich (campestanol to sitostanol ratio 1:11) and (2) campestanol ester-rich (campestanol to sitostanol ratio 1:2) rapeseed oil margarine, (3) butter, and (4) sitostanol ester-rich (campestanol to sitostanol ratio 1:13) butter. The respective scheduled stanol intake was 3.18, 3.16, and 2.43 g/d. The 6-week margarine periods and, after an 8-week washout, 5-week butter periods were double-blind and in random order. Serum cholesterol precursor sterols (indicators of cholesterol synthesis) and plant sterols (indicators of cholesterol absorption) were quantified with gas-liquid chromatography (GLC). Low-density lipoprotein (LDL) cholesterol was reduced by 8% and 10% with the sitostanol and campestanol ester-rich margarines versus baseline (P < .05 for both) and high-density lipoprotein (HDL) cholesterol was increased by 6% and 5% (P < .05), so the LDL/HDL cholesterol ratio was reduced by 15% (P < .05 for both). Sitostanol ester-rich butter decreased LDL cholesterol 12% and the LDL/HDL cholesterol ratio 11% (P < .05 for both) versus the butter period. The serum proportions of plant sterols and cholestanol were similarly reduced and those of cholesterol precursor sterols were similarly increased during all periods (P < .05 for all). Serum proportions of sitostanol and campestanol were slightly increased, indicating that their absorption related to their dietary intake. During all stanol interventions, serum vitamin D and retinol concentrations and alpha-tocopherol to cholesterol ratios were unchanged, whereas those of alpha- and beta-carotenes were significantly reduced. We conclude that varying the campestanol to sitostanol ratio from 1:13 to 1:2 in margarine and in butter similarly decreased cholesterol absorption, LDL cholesterol, and the LDL/HDL cholesterol ratio such that the serum lipids became less atherogenic.

Absorption↗
PubMed1999

Nutrition.

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Cholesterol, LDL↗
PubMed1999

Regulation of cholesterol metabolism by dietary plant sterols.

Renewal has occurred in the use of plant sterols for the treatment of hypercholesterolemias. A novel development was to convert plant sterols to corresponding stanols and esterify them to fat soluble form. In contrast to the crystalline plant sterols or stanols, plant stanol esters can be easily consumed during normal food intake in soluble form in different fat-containing food constituents when they have a potent cholesterol-lowering effect, shown in normo- and hypercholesterolemic men and women without or with coronary heart disease, children and diabetes. Cholesterol lowering is approximately 10% for total and 15% for LDL cholesterol, with the respective values for stanol ester margarine (2-3 g/day stanols) being 15% and 20%. Stanol esters reduce cholesterol absorption efficiency by up to 65%, increase cholesterol elimination in feces as cholesterol itself, usually not as bile acids, and stimulate cholesterol synthesis. Serum beta-carotene level is lowered, but no fat malabsorption or lowering of serum fat soluble vitamins have been observed. In contrast to plant sterols, stanols and their esters are minimally absorbed and they reduce serum plant sterol concentrations, also preventing statin-induced increase of plant sterols. Stanol ester margarine has been included in dietary treatment of hypercholesterolemia followed by the addition of drug treatment in resistant cases.

Child↗
PubMed1999

Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population.

We investigated the changes of cholesterol and non-cholesterol sterol metabolism during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects. Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2 or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas-liquid chromatography. The latter showed a small increase in sitostanol peak during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol proportions to cholesterol were significantly reduced by 5-39% (P < 0.05 or less for all) by stanol esters; the higher their baseline proportions the higher were their reductions. The precursor sterol proportions were significantly increased by 10- 46%, and their high baseline levels predicted low reduction of serum cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6-month feeding increased serum cholesterol by 5% (P < 0. 001) and serum plant sterol proportions by 8-13% (P < 0.001), but had no consistent effect on precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol exceeded that of baseline; the non-cholesterol sterol proportions suggested that stimulated synthesis with relatively weak absorption inhibition contributed to the non-responsiveness of these subjects. In conclusion, plant stanol ester feeding lowers serum cholesterol in about 88% of subjects, decreases the non-cholesterol sterols that reflect cholesterol absorption, increases the sterols that reflect cholesterol synthesis, but also slightly increases serum plant stanols. Low synthesis and high absorption efficiency of cholesterol results in the greatest benefit from stanol ester consumption.

Anticholesteremic Agents↗
PubMed1999

Impaired postprandial clearance of squalene and apolipoprotein B-48 in post-menopausal women with coronary artery disease.

It is not known in detail whether postprandial lipaemia is associated with coronary artery disease (CAD) in women. To investigate this, we administered an oral vitamin A/squalene/fat meal to 24 post-menopausal women with angiographically proven CAD who were not taking hormone replacement therapy, and to 30 healthy controls (18 without and 12 with hormone replacement therapy) to evaluate the effects of CAD on postprandial lipoprotein metabolism. This was done by assessing squalene, triacylglycerols, retinyl palmitate and apolipoprotein B-48 (apoB-48) during the subsequent 24 h. The subjects with CAD had significantly higher fasting concentrations of squalene and apoB-48 in triacylglycerol-rich lipoproteins (TGRL) compared with the controls. The postprandial areas under the incremental curve of TGRL apoB-48, chylomicrons, very-low-density lipoprotein (VLDL) and TGRL squalene, and of retinyl palmitate in VLDL only, were significantly higher in women with CAD than in controls. Adjustment for fasting values did not eliminate the differences in postprandial squalene and apoB-48 between CAD and controls. The postprandial responses of control subjects were not influenced by hormone replacement therapy. The peaks of squalene and retinyl palmitate of the controls, but not of the women with CAD, occurred significantly earlier (P<0.01 for both) in chylomicrons than in VLDL. The findings suggest that lipoproteins that accumulate postprandially are labelled by dietary squalene, and that these lipoproteins may be atherogenic in post-menopausal women.

Apolipoprotein B-48↗
PubMed1998

Fat-modified diets influence serum concentrations of cholesterol precursors and plant sterols in hypercholesterolemic subjects.

Serum noncholesterol sterols, cholesterol precursors and plant sterols, are indicators of cholesterol absorption and synthesis. Serum plant sterol concentrations correlate positively with cholesterol absorption, but have also been found to correlate with dietary unsaturated to saturated fatty acid ratios. We studied the concentration of serum noncholesterol sterols during four different fat-modified diets, (1) high-fat, saturated fat-enriched (control), (2) reduced-fat, sunflower oil-enriched (SO-enriched), (3) rapeseed oil-enriched (RO-enriched), and (4) reduced-fat, saturated fat-enriched (reduced-fat), followed for 6 months in hypercholesterolemic subjects in a parallel design. The proportion of lathosterol (micrograms per 100 mg cholesterol), a precursor of cholesterol synthesis, increased significantly (P < .05) in both SO-enriched (mean +/- SD 147 +/- 57 v 167 +/- 76, 0 v 6 months) and RO-enriched (147 +/- 54 v 157 +/- 52) groups, where the reduction in low-density lipoprotein (LDL) cholesterol was also significant. The proportion of sitosterol, a plant sterol, decreased significantly in the control group (137 +/- 48 v 122 +/- 42), and the proportion of another plant sterol, campesterol, increased in the RO-enriched group (280 +/- 141 v 333 +/- 162), reflecting changes in the use of vegetable oils in these two groups rather than increased cholesterol absorption. In the whole study population, the proportion of linoleic and alpha-linolenic acid (a marker of the use of RO) in cholesterol esters (CEs) correlated (P < .001) with the proportion of sitosterol (r = .43) and campesterol (r = .36) in serum at the end of the study. In conclusion, serum cholesterol precursors were found to be useful indicators of cholesterol metabolism, but changes in serum plant sterols reflected dietary changes rather than cholesterol metabolism during long-term dietary intervention with fat-modified diets.

Adult↗
PubMed1998

Oral guar gum treatment of intrahepatic cholestasis and pruritus in pregnant women: effects on serum cholestanol and other non-cholesterol sterols.

BACKGROUND: Our aim was to investigate whether intestinal binding of bile acids by guar gum, a dietary fibre, relieves cholestasis and pruritus in intrahepatic cholestasis of pregnancy. METHODS: Forty-eight pregnant women with cholestasis and pruritus were randomized double-blind to guar gum and placebo until the time of delivery, and 20 healthy pregnant women were used as control subjects. The pruritus score and serum bile acids, lipids and non-cholesterol sterols were measured at baseline, at least 2 weeks after treatment, just before delivery and up to 4 weeks after delivery. RESULTS: The increase in serum bile acids and worsening of pruritus were prevented by guar gum in relation to placebo (P < 0.05). Serum cholesterol was unchanged, but increased cholesterol precursor sterol values suggested that cholesterol synthesis was increased by guar gum. Serum cholestanol proportion, an indicator of cholestasis, was related to pruritus but was unaffected by guar gum. CONCLUSION: We conclude that in intrahepatic cholestasis of pregnancy and pruritus, guar gum treatment is beneficial in relieving pruritus, even although indicators of cholestasis are only partially reduced.

Administration, Oral↗
PubMed1998

Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels.

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.

Adult↗
PubMed1998

The apolipoprotein E phenotype has a strong influence on tracking of serum cholesterol and lipoprotein levels in children: a follow-up study from birth to the age of 11 years.

The extent to which an individual maintains his position relative to the rest of the population is called tracking. The objective of this study was to examine the effect of the apolipoprotein E (apoE) phenotype on the tracking of serum cholesterol and lipoproteins from birth to the age of 11 y. In a longitudinal follow-up study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193), and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 mo (n = 196), and 5 (n = 162) and 11 y (n = 153). Concentrations of total HDL, HDL2, and HDL3, VLDL, and LDL cholesterol were determined at 2, 6, 9, and 12 mo (n = 36), and 5 (n = 162) and 11 y (n = 153). The apoE phenotype was determined in 151 children. The children had the following apoE phenotypes: 4 had type 4/4 and 40 type 3/4 (group apoE4), 94 had type 3/3 (group apoE3), and 11 had type 2/3 and 2 type 2/4 (group apoE2). The correlation coefficients for total cholesterol levels during childhood compared with the level at 11 y of age were: 0.03 at birth, 0.26 (p < 0.001) at 2 mo, 0.24 (p < 0.001) at 4 mo, 0.24 (p < 0.001) at 6 mo, 0.28 (p < 0.001) at 9 mo, 0.41 (p < 0.001) at 12 mo, and 0.60 (p < 0.001) at 5 y. When the children were divided into three groups according to their apoE phenotypes, these three groups had the following correlation coefficients at 4 mo, 12 mo, or 5 y of age compared with the level at the age of 11 y; group apoE2: r = 0.65 (p < 0.01), r = 0.59 (p < 0.01), and r = 0.72 (p < 0.01); group apoE3: r = 0.27 (p < 0.01), 0.43 (p < 0.001), and r = 0.64 (p < 0.001); and group apoE4: r = 0.14 (p = NS), r = 0.33 (p < 0.05), and 0.42 (p < 0.01). The apoE phenotype also strongly influenced the tracking of the LDL cholesterol levels; the correlation coefficients between 5 and 11 y of age were for group apoE2 r = 0.84 (p < 0.001), for group apoE3 r = 0.70 (p < 0.001), and for group apoE4 r = 0.37 (p < 0.05). Our results indicate that the apoE phenotype strongly influences the tracking of lipids. The children having apoE 2/3, 2/4, and 3/3 phenotypes maintained their relative cholesterol and lipoprotein levels better than the others throughout the first 11 y of age. Because the apoE phenotype strongly affects the tracking of serum cholesterol, the usefulness of cholesterol screening in predicting future cholesterol values should be analyzed, keeping the apoE phenotype in mind.

Apolipoproteins E↗
PubMed1997

Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine: women and dietary sitostanol.

BACKGROUND: Reduction of serum cholesterol decreases mortality in primary and especially in secondary prevention. We investigated how effectively postmenopausal women with a previous myocardial infarction reduced their serum cholesterol with dietary means by using sitostanol ester rapeseed oil margarine, alone and in combination with statins, and to what extent cholesterol metabolism was affected. METHODS AND RESULTS: The first study group consisted of 22 randomly chosen women with angiographically documented coronary artery disease. Baseline studies on home diet were followed by double-blind, randomized, cross-over studies on margarine without and with sitostanol (3 g/d) ester for 7 weeks in random order. A second group of 10 women on simvastatin consumed sitostanol ester margarine for 12 weeks. Sitostanol ester margarine lowered serum total cholesterol by 13% (P<.05) and LDL cholesterol by 20% (P<.01). Sitostanol ester margarine reduced total cholesterol in all patients, LDL cholesterol <2.6 mmol/L (<100 mg/dL) in 32%, and <3.4 mmol/L (<133 mg/dL) in 73% versus none and 27% during the home diet (P<.01 for both). Combined with simvastatin, sitostanol still reduced total and LDL cholesterol by 11+/-3% and 16+/-5% (P<.01 for both). Sitostanol reduced absorption (-45%), increased fecal elimination (+45% as neutral sterols), and stimulated synthesis (+39%) of cholesterol. High cholestanol and plant sterol (high cholesterol absorption) and low baseline precursor sterol proportions (low cholesterol synthesis) predicted high decreases in serum cholesterol. CONCLUSIONS: Dietary use of sitostanol ester margarine normalizes LDL cholesterol in about one third of women with previous myocardial infarction, especially in those with high baseline absorption and low synthesis of cholesterol, and in combination with statins reduces the needed drug dose.

Absorption↗
PubMed1997

The effects of ursodeoxycholic acid on serum and biliary noncholesterol sterols in patients with gallstones.

Litholytic bile acid ursodeoxycholic acid (UDCA) reduces biliary cholesterol secretion and alters cholesterol metabolism by mechanisms that are not fully understood. To evaluate cholesterol metabolism during UDCA treatment, we studied serum and biliary lipids and cholesterol precursor sterols (lanosterol and other dimethyl and monomethyl sterols, lathosterols, and desmosterol), indicators of cholesterol synthesis, and plant sterols campesterol and sitosterol, indicators of cholesterol absorption, before and during administration of UDCA, 9 mg/kg/d, for 26 weeks in eight patients with radiolucent gallstones. During UDCA administration, serum lipid concentrations were unchanged, but the biliary concentration and molar percentage of cholesterol were markedly decreased. The proportions of the cholesterol precursor sterols to cholesterol were significantly interrelated between serum and bile before and especially during UDCA administration. Lanosterol and lathosterol levels, especially in bile, were significantly decreased by 43% and 34%, suggesting that UDCA may inhibit cholesterol synthesis. Levels of the other methylated precursor sterols were increased in serum and bile. The esterification percentages of all sterols were unchanged. The plant sterol-to-cholesterol ratios increased significantly in serum and bile, and there was an inverse correlation between the increment of serum plant sterols and decreased biliary molar percentage of cholesterol. In conclusion, UDCA may inhibit cholesterol synthesis possibly at the squalene synthase or 4alpha-demethylase steps, resulting in decreased biliary secretion of cholesterol. Reduced biliary sterol secretion probably increased serum plant sterol levels, indicating that under these conditions they no longer reflect the intestinal efficiency of cholesterol absorption.

Bile↗
PubMed1997

Expression and therapeutic response related to apolipoprotein E polymorphism in primary biliary cirrhosis.

BACKGROUND/AIMS/METHODS: Apolipoprotein E polymorphism, affecting intestinal absorption and biliary secretion of bile acids, might also contribute to the variable course and response to drug treatment of primary biliary cirrhosis. To test this possibility, we studied the apo E gene frequency, and the expression and response to drug therapy in different apo E isoforms of 88 patients with primary biliary cirrhosis, randomized to ursodeoxycholic acid, colchicine or placebo treatments for 2 years. RESULTS: The frequency of the epsilon2 allele was 2.4 times higher (p<0.01) in the patients with primary biliary cirrhosis compared with the Finnish population. At entry the patients with the epsilon4 allele were significantly younger (p<0.01) than those with other epsilon alleles, while the severity of primary biliary cirrhosis was similar in the three apolipoprotein E phenotypes. Liver enzymes, acute hepatic inflammation, serum total and low density lipoprotein cholesterol were decreased by ursodeoxycholic acid only in the patients with the epsilon4 and homozygous epsilon3 alleles, but not in those with the epsilon2 allele. Improvements of liver enzyme tests by ursodeoxycholic acid were more marked in the patients with the epsilon4 than other epsilon alleles. CONCLUSIONS: The present data show that in primary biliary cirrhosis the epsilon2 allele is overrepresented, and suggest that the expression of primary biliary cirrhosis and response of the disease to ursodeoxycholic acid treatment are closely related to the apo E polymorphism.

Adult↗
PubMed1997

Treatment of lipid disorders in non-insulin-dependent diabetes mellitus.

The basis for treatment of lipid disorders in patients with non-insulin-dependent diabetes mellitus is weight reduction by diet and exercise, and additional control of glycaemic condition with oral antidiabetics, alone or in combination with insulin. Hypercholesterolaemic, mildly hypertriglyceridaemic non-insulin-dependent diabetes mellitus patients respond to cholesterol malabsorption caused by dietary sitostanol ester margarine, while long-term statin treatment of respective coronary patients significantly lowers the recurrence of coronary events, in addition to improving the lipid disorder. However, no information is available concerning the preventive effect of long-term improvement of lipid disorders in non-insulin-dependent diabetes mellitus patients without coronary heart disease, or in patients with the 'classical' type of diabetic lipid disorder, that is, hypertriglyceridaemia with low HDL and normal-low LDL-cholesterol levels. In this group of patients, beneficial lipid effects can be obtained (although perhaps not normalization) with fibrates alone or, especially, in combination with current statins.

Anticholesteremic Agents↗
PubMed1997

Polymorphisms of the genes encoding apoproteins A-I, B, C-III, and E and LDL receptor, and cholesterol and LDL metabolism during increased cholesterol intake. Common alleles of the apoprotein E gene show the greatest regulatory impact.

Genetic and dietary factors regulate serum cholesterol level, but detailed investigations into their interactions have not been established. We assessed the effects of apoprotein (apo) E phenotype and polymorphic alleles of the apo A-I, apo B, apo C-III, and LDL receptor genes, separately and together, on regulation of serum LDL cholesterol level. The study group consisted of 29 middle-aged men, and cholesterol absorption, bile acid, and cholesterol synthesis and LDL apo B kinetics were studied in these men during low- and high-cholesterol diets. The six apo B alleles were identified on the basis of Xba I, EcoRI, and Msp I restriction fragment length polymorphism (RFLP), the apo A-I alleles with the Msp I RFLP, and the apo C-III and LDL receptor alleles corresponded to the Sst I and PvuII RPLPs of these genes, respectively. During low cholesterol intake, LDL cholesterol levels were similar in all of the genetic groups except for men with apo E2 phenotype. They had significantly (P < .05) lower levels of LDL apo B and cholesterol than men without the epsilon 2 allele. The low values were caused by a significantly higher removal of LDL apo B (apo E2, 0.453 +/- 0.03 versus apo E3, 0.312 +/- 0.01 pools per day, P < .05). High cholesterol intake increased LDL cholesterol levels in all genetic categories except in the apo E2 phenotype irrespective of the combinations with other polymorphisms. Carriers of the apo B R+ allele (EcoRI site present) presented with the most prominent LDL cholesterol rise (from 2.71 +/- 0.14 to 3.37 +/- 0.29 mmol/L). In multiple stepwise regression analysis, apo B EcoRI RFLP and apo E phenotypes were the only variables that explained the variability of high cholesterol intake-induced change in LDL cholesterol levels. In summary, in any genetic combination, individuals with the epsilon 2 allele had the lowest LDL cholesterol values and were nonresponders to dietary cholesterol, whereas subjects with the apo B R+ allele had marked LDL elevations, especially in combination with the epsilon 4.

Alleles↗